62P - Role of IL6 (C-174G) polymorphism in the development of cervical intraepithelial neoplasia

Background

Cervical intraepithelial neoplasia (CIN) is regarded as a precancerous condition of the cervix. The tumor microenvironment contains a large number of immune cells, in particular, tumor-associated neutrophils (Nph), as well as pro-inflammatory cytokines, including IL6, which causes chronic inflammation and immunosuppression. The role of IL6 in the onset and progression of CIN has been shown (Chen J, Wang L, 2022). Regulation of cytokine expression occurs at the transcriptional level, in the promoter region of the gene. For IL6, a single nucleotide polymorphism (SNP) with a substitution at position -174G→C has been described that is associated with the risk of breast cancer. IL6 polymorphism (rs2069837) is significantly associated with an increased risk of cervical cancer (Das AP, et al, 2022). However, there is no data on the involvement of SNP IL6 C-174G (rs1800795) in the occurrence and development of CIN. The aim of the study was to evaluate the role of IL6 (C-174G) polymorphism in the development of CIN.

Methods

The study included 60 patients diagnosed with high-grade squamous intraepithelial lesions (CIN II, CIN III and cancer in situ) and 30 somatically healthy women (control). The study was conducted in accordance with the requirements of the ethics commission of UlSU. The level of IL6 was determined in Nph lysate by ELISA method (Vector-Best, Russia). The presence of SNP IL6 C-174G was assessed by polymerase chain reaction with restriction enzyme analysis using RsaI endonuclease (SibEnzyme, Russia). Electrophoresis was carried out in 1.5% agarose gel. Statistical processing was carried out using Statistica 13.

Results

It was found that the -174G* allele is more common in the group with lesions of the cervix (75.7%) than in the control (53.3%). The risk of developing CIN increased with an increase in the level of IL6 in Nph with CIN (9.69 (6.89-10.85) vs 1.33 (0.78-2.25), p=0.015) and the presence of the -174G allele * (OR=0.411, 95% CI 0.220-0.768, p=0.005) (χ2=23.4, p=0.001).Simultaneous assessment of the level of IL6 in Nph and SNP IL6 C-174G allows predicting the development of CIN with sensitivity (0.769) and specificity (0.897).

Conclusions

The presence of IL6 polymorphism (C-174G) and an elevated level of IL6 in Nph indicate the possibility of CIN.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.